Logo

American Heart Association

  110
  0


Final ID: Th0081

Chronic Alcohol Consumption Amplifies Intramuscular Oxidative Stress And Mitochondriopathy In Patients With Peripheral Artery Disease

Abstract Body: Alcohol abuse and peripheral artery disease (PAD) are independent contributors to skeletal muscle damage; both characterized by mitochondriopathy. We recently showed that muscle structural damage is exacerbated in PAD patients with a history of heavy alcohol use, however, potential underlying mechanisms remain unexplored. Methods: We compared key markers of oxidative stress and mitochondrial electron transport chain (ETC) abundance in gastrocnemius muscle biopsies from PAD patients with heavy alcohol use (>14 or > 7 drinks/week, for males and females, respectively, n = 7) with PAD patients (n = 6) and non-PAD controls (n = 5) consuming moderate to low or no alcohol. The intramuscular content of alcohol dehydrogenase 1B (ADH1B), responsible for alcohol catabolism to reactive aldehydes, and aldehyde dehydrogenase 2 (ALDH2), which subsequently degrades toxic aldehydes, were also assessed. Results: Irrespective of drinking status, muscle oxidative stress (4-hydroxynonenol (4-HNE) and protein carbonyls) was significantly greater in PAD patients compared to non-PAD controls (P < .01). Mitochondrial ETC Complex I (CI) protein was also reduced in PAD muscle (P = .0008). Nevertheless, 4-HNE accumulation (P = .0002) and the extent of ETC CI loss (P = .0373) was significantly greater in heavy-drinking PAD (PAD-HD) patients compared to low to moderate drinkers (PAD-LD). The loss of ETC components was also more extensive in PAD-HD muscle and included reductions in all five complexes (P < .05). When the alcohol-metabolizing enzymes were assessed, PAD-HD muscle only showed a significant increase in ADH1B compared to control (P = .0314) and PAD-LD muscle (P = .0423). Interestingly, ALDH2 was unaltered in PAD-HD patients (P = .7777). but was significantly increased in PAD-LD compared to controls (P = .0041) and PAD-HD (P = .0087). Conclusions: Although traditionally known for regulating the breakdown of alcohol-derived toxic metabolites, ALDH2 also plays a key role in the removal of other reactive aldehydes, including those generated consequent to mitochondrial oxidative stress, such as 4-HNE and protein carbonyls. Considering ALDH2 was higher, and 4-HNE and ETC complex loss was lower in PAD-LD patients, an alcohol-derived dysfunction in ALDH2 may account for why intramuscular oxidative stress and mitochondriopathy was more extensive in PAD patients with heavy alcohol use. Thus, ALDH2 could be a promising therapeutic target to mediate oxidative stress in PAD patients.
  • Fletcher, Emma  ( University of West Florida , Pensacola , Florida , United States )
  • Miserlis, Dimitrios  ( UT Austin Dell Med School , Austin , Texas , United States )
  • Papoutsi, Evlampia  ( University of West Florida , Pensacola , Florida , United States )
  • Pipinos, Iraklis  ( UNIV NEBRASKA MEDICAL CTR , Omaha , Nebraska , United States )
  • Koutakis, Panagiotis  ( University of West Florida , Pensacola , Florida , United States )
  • Author Disclosures:
    Emma Fletcher: DO NOT have relevant financial relationships | Dimitrios Miserlis: DO NOT have relevant financial relationships | Evlampia Papoutsi: DO NOT have relevant financial relationships | Iraklis Pipinos: DO have relevant financial relationships ; Research Funding (PI or named investigator):MitoQ LLC:Active (exists now) ; Research Funding (PI or named investigator):Novo Nordisk A/s:Active (exists now) | Panagiotis Koutakis: DO NOT have relevant financial relationships
Meeting Info:
Session Info:

15. Poster Session 3 & Reception

Thursday, 04/24/2025 , 05:00PM - 07:00PM

Poster

More abstracts on this topic:
4-Hydroxy-2-Nonenal Alters Alternative Polyadenylation to Regulate mRNA Isoform Diversity in the Transition from Human Cardiac Fibroblasts to Myofibroblasts

Natarajan Kartiga, Neupane Rahul, Yalamanchili Hari Krishna, Palaniyandi Suresh, Wagner Eric, Guha Ashrith, Amirthalingam Thandavarayan Rajarajan

Circulating Metabolomic Biomarkers of 5-Year Unintentional Weight Loss in a Biracial Community-Dwelling Older Cohort

Yao Shanshan, Marron Megan, Miljkovic Iva, Farsijani Samaneh, Tseng George, Shah Ravi, Murthy Venkatesh, Newman Anne

More abstracts from these authors:
Muscle Oxygen Levels in Patients with Claudication: Measurements During Rest, Walking, and Temporary Oocclusion of Blood Flow

Tian Yuqian, Pipinos Iraklis, Anderson Cody, Hakim Ali, Sharma Prateek, Bajaj Varnica, Despiegelaere Holly, Myers Sara, Koutakis Panagiotis, Park Song-young

Multi-omics Approach of Peripheral Artery Disease Patient Gastrocnemius Describes Disease Progression

Miserlis Dimitrios, Fletcher Emma, Papoutsi Evlampia, Pipinos Iraklis, Koutakis Panagiotis

You have to be authorized to contact abstract author. Please, Login
Not Available